Mutation landscape of germline and somatic BRCA1/2 in patients with high-grade serous ovarian cancer

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors targeting BRCA1/2 mutations are available for treating patients with high-grade serous ovarian cancer. These treatments may be more appropriately directed to patients who might respond if the tumor tissue is additionally tested by next-generation sequencing with a multi-gene panel and Sanger sequencing of a blood sample. In this study, we compared the results obtained using the next-generation sequencing multi-gene panel to a known germline BRCA1/2 mutational state determined by conventional Sanger sequencing to evaluate the landscape of somatic mutations in high-grade serous ovarian cancer tumors. METHODS: Cancer tissue from 98 patients with high-grade serous ovarian cancer who underwent Sanger sequencing for germline BRCA1/2 analysis were consecutively analyzed for somatic mutations using a next-generation sequencing 170-gene panel. RESULTS: Twenty-four patients (24.5%) showed overall BRCA1/2 mutations. Seven patients (7.1%) contained only somatic BRCA1/2 mutations with wild-type germline BRCA1/2, indicating acquired mutation of BRCA1/2. Three patients (3.1%) showed reversion of germline BRCA1 mutations. Among the 14 patients (14.3%) with both germline and somatic mutations in BRCA1/2, two patients showed different variations of BRCA1/2 mutations. The next-generation sequencing panel test for somatic mutation detected other pathogenic variations including RAD51D and ARID1A, which are possible targets of poly (ADP-ribose) polymerase inhibitors. Compared to conventional Sanger sequencing alone, next-generation sequencing-based tissue analysis increased the number of candidates for poly (ADP-ribose) polymerase inhibitor treatment from 17.3% (17/98) to 26.5% (26/98). CONCLUSIONS: Somatic mutation analysis by next-generation sequencing, in addition to germline BRCA1/2 mutation analysis, should become the standard of care for managing women with high-grade serous ovarian cancer to widen the indication of poly (ADP-ribose) polymerase inhibitors.ope

패혈증 비브리오균에서 포도당 유무에 따른 HPr의 pyruvate kinase A 활성 조절

학위논문 (박사)-- 서울대학교 대학원 : 생명과학부, 2015. 2. 석영재.The bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS) consists of two general proteins (enzyme I and histidine phosphocarrier protein) and several sugar-specific enzyme IIs (EIIs). In the case of the glucose PTS, EII consists of the cytoplasmic enzyme IIAGlc (EIIAGlc) and the membrane associated enzyme IICBGlc (EIICBGlc). During the uptake of glucose, the phosphoryl group is transferred from phosphoenolpyruvate (PEP) to glucose in order of PEP → enzyme I (EI) → histidine phosphocarrier protein (HPr) → EIIAGlc → EIICBGlc → glucose. In addition to the phosphorylation-coupled transport of sugars, PTS proteins participate in various physiological processes through protein-protein interaction depending on their phosphorylation state. Vibrio vulnificus is an opportunistic human pathogen that causes severe and often fatal infections in susceptible individuals. Although regulatory roles of the PTS have been extensively studied in Escherichia coli, much less is known about the Vibrio vulnificus PTS. To elucidate regulatory roles of the V. vulnificus PTS, ligand fishing was performed using HPr as bait. A HPr-binding protein in V. vulnificus was revealed as an ortholog of E. coli pyruvate kinase A (ePykA), and it was named a vPykA standing for Vibrio pyruvate kinase A. Pyruvate kinase (PK) catalyzes the final step of glycolysis, which is the transfer of a phosphoryl group from PEP to ADP, generating the products ATP and pyruvate for anaerobic and aerobic metabolism. The interaction between HPr and vPykA was strictly dependent on the presence of inorganic phosphate, and only dephosphorylated HPr interacted with vPykA. Experiments involving domain swapping between the PykAs of V. vulnificus and E. coli revealed the requirement for the C-terminal domain of vPykA for a specific interaction with V. vulnificus HPr. Because the binding site for the allosteric effector is located at the C-terminal domain of PKs and the C-terminal domain determines the specificity of the HPr-vPykA interaction, the effect of HPr as an allosteric regulator of vPykA was assessed by a lactate dehydrogenase (LDH)-coupled enzyme assay. Only dephosphorylated HPr decreased the Km of vPykA for PEP by approximately four-fold without affecting Vmax. To elucidate physiological roles of vPykA, the vPykA-deficient mutant (pykA mutant) was constructed. the pykA mutant cells entered the viable but nonculturable (VBNC) state much faster than wild-type cells when 5 x 106cells of each of the two strains were incubated in Luria-Bertani medium containing 2.5% NaCl (LBS) at 4°C. Several studies have provided evidence for the involvement of reactive oxygen species (ROS) in the VBNC state of V. vulnificus by showing that a significant portion of the VBNC population of V. vulnificus can be resuscitated if H2O2 scavenger (catalase or pyruvate) is present in the culture medium. Interestingly, a pykA mutant was more susceptible to H2O2 than wild-type V. vulnificus, and this sensitivity was completely rescued by the addition of pyruvate to the culture medium. Here, it is shown that V. vulnificus dephospho-HPr increases the affinity of vPykA for PEP to confer resistance to H2O2 stress in the presence of a PTS sugar, such as glucose.CONTENTS ABSTRACT …………………………………………………………i CONTENTS ………………………………………………………v LIST OF FIGURES ………………………………………………xi LIST OF TABLES ………………………………………………xiv ABBREVIATIONS ………………………………………………xv CHAPTER I. Introduction ………………………………………1 1. Epidemiology and pathogenesis of Vibrio vulnificus ……2 1.1. Overview of V. vulnificus ………………………………2 1.2. Epidemiology of V. vulnificus …………………………3 1.2.1. Types of infection and disease …………………3 1.2.2. Host susceptibility …………………………………4 1.2.3. Clinical symptoms and treatment ………………5 1.3. Virulence factors of V. vulnificus ………………………7 1.3.1. Polysaccharide capsule …………………………7 1.3.2. LPS ……………………………………………………8 1.3.3. Pili ……………………………………………………9 1.3.4. Hemolysins …………………………………………9 1.3.5. Metalloprotease ……………………………………12 1.3.6. Iron …………………………………………………13 1.4. Viable but non-culturable state in V. vulnificus ……14 1.4.1. Characteristics of viable but non-culturable cells …………………………………………………14 1.4.2. The occurrence of VBNC cells and their importance …………………………………………16 2. Phosphoenolpyruvate:sugar phosphotransferase system ………………………………………………………………………17 2.1. Overview of phosphoenolpyruvate:sugar phosphotransferase system in Escherichia coli …17 2.2. Components of glucose PTS in E. coli ……………19 2.3. PTS-mediated regulation in E. coli …………………22 2.3.1. Glucose PTS-mediated regulations …………23 2.3.2. Carbon catabolite repression …………………23 2.3.3. Inducer exclusion …………………………………25 2.3.4. Regulation of adenylate cyclase activity by EIIAGlc ………………………………………………26 2.3.5. Regulation of FrsA by EIIAGlc …………………27 2.3.6. Interaction between acetate kinase and EI …28 2.3.7. Interaction between glycogen phosphorylase and HPr ……………………………………………29 2.3.8. Interaction between anti-σ70 factor Rsd and HPr …………………………………………………30 2.4. PTS in V. vulnificus ……………………………………30 2.5. PTS-mediated regulation in V. vulnificus ……………34 2.5.1. Interaction between Vibrio insulin degrading enzyme (vIDE) and EIIAGlc ……………………34 3. Pyruvate kinase in glycolytic pathway ……………………35 3.1. Regulatory and functional properties of pyruvate kinase ……………………………………………………35 3.2. Characterization of bacterial pyruvate kinases ……37 4. Aims of this study ……………………………………………39 CHAPTER II. Materials and Methods ………………………40 1. Construction of bacterial strains and plasmids …………41 1.1. Deletion of vPykA gene …………………………………41 1.2. Complementation of the vpykA mutant ………………42 1.3. Construction of chimeric PykA proteins ……………42 2. Media and cell culture ………………………………………49 3. Protein purification ……………………………………………49 4. Ligand fishing to search for proteins interacting with H-vHPr ………………………………………………………………50 4.1. Ligand fishing using protein bait ………………………50 4.2. In gel-digestion …………………………………………53 5. RNA isolation and qRT-PCR ………………………………53 6. Surface plasmon resonance spectroscopy ……………54 7. Measurement of pyruvate kinase activity ………………55 8. Determination of the in vivo phosphorylation state of vHPr ………………………………………………………………………57 9. Determination of the intracellular PEP and pyruvate concentrations ……………………………………………………58 CHAPTER III. Results ……………………………………………60 1. Specific interaction between HPr and pyruvate kinase A in Vibrio vulnificus ………………………………………………61 1.1. Ligand fishing using V. vulnificus HPr as bait ……61 1.2. Ligand fishing using vPykA as bait …………………67 1.3. Dependence of the interaction between vHPr and vPykA on inorganic phosphate ………………………69 1.4. Confirmation of the interaction between vHPr and vPykA by surface plasmon resonance (SPR) ……75 1.5. Phosphorylation state-dependent interaction between vHPr and vPykA ………………………………77 1.6. The C-terminal domain of vPykA determines the binding specificity of the vHPr-vPykA complex ……81 2. Effect of vHPr on vPykA activity ……………………………88 2.1. Allosteric effect between PKs and HPr proteins ……88 2.2. The phosphorylation state of vHPr is important for the regulation of vPykA activity ……………………………92 3. In vivo effect of the vHPr–vPykA interaction ………………97 3.1. The in vivo phosphorylation state of vHPr …………97 3.2. Phosphorylation state-dependent effect of vHPr on vPykA activity is dependent on the presence of glucose ……………………………………………………99 3.3. Phenotypes of pykA deletion mutant ………………105 3.4. vPykA activity confers resistance to H2O2 …………109 4. The essentiality of the gene coding for the vPykF ……115 CHAPTER IV. Discussion ……………………………………117 국문초록 …………………………………………………………149Docto

A Study on the Characteristics of Nanofluid on Heat Transfer and Nano-molecular Motions at the Liquid-Vapor Interface

Traditional heat transfer fluid has a heat transfer characteristic which is worse than that of the solid although many studies have been conducted to increase heat transfer in fluid. One of the various heat transfer enhancement techniques is to suspend fine metallic or nonmetallic solid powder in traditional fluid. Nanofluid is defined at a new kind of heat transfer fluid containing a very small quantity of nanometer particles that are uniformly and stably suspended in a liquid. In this study, CuNi or CuAg nano particles are used to investigate heat transfer enhancement. Through the molecular dynamic(MD) method, molecular behavior was clarified on an interface to examine the heat transfer mechanism of nanofluid in a molecular dynamics point of view . The result showed that the thermal conductivity of 0.5vol% CuNi nanopowder in ethyleneglycol solution was 124% higher than that of ethyleneglycol solution only. By the numerical analysis for the molecular motions at the liquid-vapor interface, a criterion to distinguish between liquid and vapor was suggested by a potential energy and the number of neighboring molecules. When a molecule moved into a vapor region from a liquid region, the potential energy of a molecule was increased but the number of neighboring molecules was decreased.List of tables List of figures Abstract 1. 서론 = 1 1.1 연구의 배경 = 1 1.2 기존의 연구 = 3 1.3 연구의 목적 = 5 2. 나노 구리합금분말을 혼합한 용액이 열전달에 미치는 영향 = 6 2.1 나노유체의 열전달 특성 = 6 2.1.1 금속의 높은 열전도 성질 = 6 2.1.2 나노유체의 냉각 메커니즘의 제시 = 9 2.2 실험방법 = 12 2.2.1 비정상열선법 이론 = 12 2.2.2 실험장치 및 조건 = 14 2.3 실험결과 및 고찰 = 20 3. 분자동역학법을 이용한 기액계면에서의 분자거동에 관한 고찰 = 25 3.1 분자동역학법 = 25 3.1.1 Lennard-Jones potential = 28 3.1.2 뉴턴의 운동방정식 = 31 3.1.3 운동방정식의 적분 = 32 3.2 계산조건 및 방법 = 34 3.2.1 주기경계조건(Periodic boundary condition) = 34 3.2.2 온도제어 방법 = 37 3.2.3 계산계 = 39 3.3 계산결과 및 고찰 = 42 4. 결론 = 53 참고문헌 = 5

산업혁신시스템(SSI) 관점에서

학위논문(석사) -- 서울대학교대학원 : 자연과학대학 협동과정 과학사 및 과학철학전공, 2022.2. 박상욱.본 연구는 한국 바이오제약 산업의 형성과 진화 과정을 Franco Malerba가 주창한 산업혁신시스템(Secotral System of Innovation, SSI) 관점을 적용하여 추적했다. 산업화 후발주자로서 성공적인 선진국 추격을 완성한 한국에서는 1980년대 중반에 바이오제약 산업이 태동했으며 약 40여 년이 지난 현재에는 바이오제약 산업 선도국과의 산업경제적 격차를 해소하면서 세계적인 주요 산업 플레이어로 인정받기 시작했다. 40여 년의 한국 바이오제약 산업 발달 과정은 한 국가 내에서의 새로운 산업의 등장과 성숙으로 이해할 수 있으며 이 과정은 산업의 고유한 특성과 산업의 동태적 진화를 동시에 분석할 수 있는 관점인 산업혁신시스템을 통해 효과적으로 파악할 수 있다. 본 연구는 바이오제약 산업혁신시스템의 구성요소를 파악해 각 요소의 개별적, 상호작용적 진화를 확인함으로써 한국 바이오제약 산업의 행위자들이 산업의 제도적 틀을 형성하고 상호작용하며 역량을 강화해온 과정에서 나타난 특징을 보고했다. 한국에서의 바이오제약 산업의 형성과 진화는 유례가 없는 추격 사례이다. 산업화 후발국이 과학기반 산업인 바이오제약 산업에 대해서도 성공적으로 추격한 경우를 찾아보기 어렵고 기존의 제조업 추격과는 다른 양상의 기술혁신이 관찰되었기 때문이다. 연구개발사업의 확대로 과학기술 역량을 축적했으며, 이전 시기의 성공 경험에서 축적된 제도적, 조직적, 산업적 자원을 동원했다. 이에 따라 본 연구는 한국 바이오제약 산업 발달을 추격을 완료한 국가에서 발생하는 산업의 추격 현상이라고 주장하며, 탈추격형 추격이라고 제안했다.This paper examines the formation and evolution of biopharmaceutical industry in Korea since 1980s. The process of development of biopharmaceutical industry in Korea over 40 years can be understood as the emergence and maturation of a new industry within a country. Since Franco Malerba’s sectoral system of innovation(SSI) perspective is an effective research framework for analyzing the evolutionary process of sectoral dynamics, this paper applies SSI to trace the biopharmaceutical industry development process. This study identifies the components of the biopharmaceutical SSI and confirms the individual and interactive evolution of each element, showing the characteristics of actors in the Korean context in the process of forming and interacting with the institutional framework of the industry and building their capabilities. It is also important to notice that the formation and evolution of the biopharmaceutical industry in Korea is an unprecedented case of catching-up. This is because it is difficult to find a case in which a latecomer of industrialization has even successfully developed the biopharmaceutical industry, which is a science-based industry. The strategies observed in this case are different from those which has been accepted as a typical innovation process of catching-up countries. Korea has accumulated scientific and technological capabilities through the expansion of R&D projects, and mobilized institutional, organizational, and industrial resources accumulated from successful experiences in the previous period. Accordingly, this study asserts that the development of the Korean biopharmaceutical industry is a industrial catching-up process occurring in a country that has completed catching-up.제 1 장 서론 1 제 2 장 선행연구 검토 7 1. 산업혁신시스템(Sectoral System of Innovation) 7 1-1. 산업혁신시스템의 제안 7 1-2. 산업혁신시스템의 적용: 바이오제약 산업을 중심으로 9 2. 바이오제약 산업의 특징 11 2-1. 과학기반 산업 12 2-2. 제도와 산업의 공진화 14 2-3. 혁신 주체 간 연계와 협력 16 3. 추격과 탈추격 18 3-1. 국가의 추격과 탈추격 18 3-2. 산업의 추격 21 제 3 장 분석틀 25 제 4 장 한국 바이오제약 산업혁신시스템 30 1. 제도(Institutions) 30 1-1. 정책 및 법률 30 1-2. 거버넌스 구조 48 1-3. 산업부문으로서의 인식론적 규범 55 2. 지식기반(Knowledge Base) 57 3. 행위자 및 네트워크 64 3-1. 공공부문 65 3-2. 민간부문 82 3-3. 정렬(Alignments) 106 4. 확산(Transfer Factors) 111 제 5 장 요약 및 결론 117 1. 한국 바이오제약 산업혁신시스템의 진화 117 2. 탈추격 국가의 추격 산업 123석

Study on Prokaryotic Community Structure in Moist Acidic Tundra Soil in Council, Alaska

학위논문 (박사)-- 서울대학교 대학원 : 생명과학부, 2016. 8. 천종식.The Arctic has gained much scientific attention because global warming is predicted to be greatest and most rapid at high latitudes. A point that should yield scientific attention might be concerned about the loss of soil organic matter (SOM), as it contributes to the positive feedback of global warming. Because a warmer climate will cause carbon stored in the soil to be released into the atmosphere via microbial decomposition. With increasing scientific attention on permafrost environments impacted by global warming, many scientists have focused on the global carbon cycle in Arctic soils observing microbial life. However, knowledge on microbial community and diversity in Arctic soil yet very lacking. Thus, this study investigated prokaryotic community structure, diversity and ecological functions in moist acidic tundra soil of Alaska through the next generation sequencing (NGS) with bioinformatics processing. Moreover, this study investigated the relationship between microbial communities and soil properties. In chapter1, a general introduction with background information on Arctic environment and on the necessity of research objectives to explain further chapters is given. In chapter 2, bacterial community structure and its relationship to soil properties in moist acidic tundra soil are described. Although various plants covered the top soil and some vegetation formed a colony, the bacterial communities were not related with vegetation types. Rather, the bacterial community could be markedly differentiated by soil depth and soil pH. The vertical structure of soil profile from active layer to permafrost was observed to be more specific. All soil properties changed along soil depth, and the soil cores were divided by the decomposition status of soil organic matter (SOM). When I observed the shift of bacterial community from active layer to permafrost, active layer could be divided into Oi, Oe and OA horizons, and permafrost was classified as A horizon. Some bacterial groups abruptly changed near the boundary separating the horizons. Briefly, Acidobacteria, Gammaproteobacteria, Planctomycetes, and WPS-2 were relatively abundant in Oi horizon, Bacteroidetes, Chloroflexi, Gemmatimonadetes, Verrucomicrobia and AD3 were abundant in Oe and OA horizons, and Actinobacteria, Bacteroidetes, Caldiserica, and Firmicutes were abundant in A horizon. In archaeal groups, Crenarchaeota accounted for approximately 80% from most soil layers. Although the relative abundance of Euryarchaeota was insignificant from total archaeal abundance, the relative abundance of Methanobacteria and Methanomicrobia increased below Oi horizon. Although many studies have emphasized the quantity of soil organic carbon, this study indicated that the soil quality is primary important factor that shapes microbial community structure as well as soil pH. In chapter 3, bacterial community in Arctic tundra soil was compared with Temperate and Tropical soils. According to a previous study, microbial community significantly interacted with specific soil properties. Thus, I identified the overall bacterial community structure and diversity between biomes, and assessed their relationship with soil properties. From the results of soil properties, Arctic soil was found to be relatively acidic and of nutrient rich environment, and Temperate and Tropical soil showed to be of low nutrient environment. Temperate soil showed highest richness and diversity, while Arctic soil showed the lowest richness and diversity. At phylum level, Acidobacteria and Alphaproteobacteria were predominant in all biomes. However, specific bacterial groups relatively abundant in each biomethe relative abundance of Verrucomicrobia and AD3 were dominant in Arctic soil, and Bacteroidetes and Betaproteobacteria were dominant in Temperate soil, and Chloroflexi, Cyanobacteria, and Ntrospirae were dominant in Tropical soil. Most dominant OTUs in all biomes play an important role in biogeochemical cycle in their habitat. Arctic and Tropical soil contained dominant OTUs, which contribute to the reducing of positive feedback of global warming. Although the sample size was limited, this study might help with advancing an understanding the biogeography of bacterial community at regional scales. The results in this study may contribute to extend our understanding about microbial community in moist acidic tundra soil, as well as help predict the microbial response to warming effect in Arctic soil.CHAPTER 1. Introduction: Microbial Ecology in Arctic Tundra Soil 1 1.1 General characteristics of Arctic soil 2 1.2 Current status of global scientific attention for Arctic soil 6 1.3 Microbial ecology in Arctic tundra soil 10 1.4 Objectives of this study 15 CHAPTER 2. Spatial Distribution of Prokaryotic Community Structure in Moist Acidic Tundra Soil 17 2.1 Horizontal and vertical distribution of bacterial community and relationships with soil properties in active layer 18 2.1.1 Introduction 18 2.1.2 Materials and Methods 21 2.1.3 Results 33 2.1.4 Discussion 70 2.2 Comparing prokaryotic community structure between active layer and permafrost 85 2.2.1 Introduction 85 2.2.2 Materials and Methods 87 2.2.3 Results 93 2.2.4 Discussion 112 CHAPTER 3. Bacterial Community Structure in Arctic Tundra and non-Arctic Soils 117 3.1 Comparison of bacterial community structure between Arctic soil and non-Arctic soil 118 3.1.1 Introduction 118 3.1.2 Materials and Methods 120 3.1.3 Results 125 3.1.4 Discussion 140 GENERAL CONCLUSIONS 143 REFERENCES 146 APPENDIX 166 국문 초록(Abstract in Korean) 177Docto

헬스리터러시의 수준과 영향요인에 대한 고찰 : 초등학생 학부모를 대상으로

학위논문 (석사)-- 서울대학교 보건대학원 : 보건학과(보건정책관리학전공), 2013. 2. 양봉민.연구목적 본 연구에서는 초등학생 학부모의 헬스리터러시 수준을 파악하고, 영향요인을 살펴보고자 한다. 이를 통해 초등학생 학부모의 헬스리터러시 향상을 위한 기초자료를 제공할 수 있다. 구체적으로는 초등학생 학부모의 헬스리터러시 수준을 파악하고, 인구사회학적 특성, 건강관련 특성, 가족 및 사회활동 특성, 일반 문해에 따른 헬스리터러시 차이를 파악하여 영향을 주는 요인을 분석한다. 이를 바탕으로 초등학생 학부모의 헬스리터러시 수준 향상을 위한 기초자료를 제공한다. 연구방법 일개 지역 초등학생 학부모의 헬스리터러시 수준을 파악하고, 영향요인을 분석하기 위한 비 실험 설계로 횡단적 서술적 조사 연구이다. 설문의 구성은 일반 문해 를 측정할 수 있는 문항과 헬스리터러시 수준을 측정할 수 있는 문항, 그리고 건강관련 특성, 가족 및 사회활동 특성, 인구사회학적 특성을 알 수 있는 문항으로 하여 이를 통해 헬스리터러시 수준과 영향요인을 알아보았다. 통계적 분석 방법으로는 빈도 분석, 변수들 간에 상관분석을 수행한 다음 특성별 헬스리터러시의 차이를 t-test/ANOVA를 통해 알아보고, 마지막으로는 변수들 간에 다중회귀분석을 실시하였다. 연구결과 연구결과 초등학생 학부모의 헬스리터러시 수준은 적절한 것으로 확인되었으며, 교육수준, 직업유무, 일반 문해에 따라 헬스리터러시 수준에 차이가 있었다. 교육수준이 높을수록, 직업이 없는 것보다 있는 집단에서, 일반 문해 수준이 높을수록 헬스리터러시 수준이 높았고, 일반 문해, 교육수준, 직업유무의 헬스리터러시에 대한 설명력은 27.6%이었으며, 일반 문해가 가장 강력한 영향요인이었다. 고찰 및 결론 초등학생 학부모의 헬스리터러시 수준은 적절한 수준인 것으로 나타났고, 대상자의 교육수준, 직업유무, 일반 문해에 따라 유의한 차이를 보였으며 이 세 요인이 초등학생 학부모의 헬스리터러시 수준에 영향을 미치는 것으로 나타났는데 그 중 일반 문해가 가장 큰 영향력을 보이는 요인으로 파악되었다. 이러한 결과는 초등학생 학부모와 같은 일반인에 있어서도 선행연구들이 주로 대상으로 삼았던 노인들과 마찬가지로 헬스리터러시 수준을 보다 향상시키기 위해 교육수준보다 일반 문해를 높일 수 있는 중재가 필요하며 이에 대상자의 교육수준, 직업유무 등의 특성을 반영할 필요가 있다는 것을 시사한다. 또한 초등학생 학부모의 헬스리터러시 수준을 보다 일반적으로 파악하기 위해 연구대상을 확대하여 반복연구를 하는 것이 필요하다. 부모가 자신의 헬스리터러시 수준 제고 뿐 아니라 그들의 자녀에게 중요한 보건교육자로서의 역할을 할 수 있도록 학교와 지역사회의 보건교육 프로그램을 제공할 필요가 있고, 현재 다양하게 번역되어 사용되고 있는 헬스리터러시에 대한 우리나라에서의 용어가 통일될 필요가 있다.Ι. 서론 1. 연구의 필요성 1 2. 연구목적 5 3. 용어정의 6 Ⅱ. 이론적 논의 1. 헬스리터러시 9 2. 헬스리터러시에 영향을 미치는 요인 15 3. 부모가 자녀의 건강에 미치는 영향 18 4. 연구의 이론적 틀 20 Ⅲ. 연구 방법 1. 연구설계 21 2. 연구대상 21 3. 연구도구 22 4. 자료수집 방법 26 5. 자료분석 방법 26 6. 연구대상자의 윤리적 고려 26 Ⅳ. 연구결과 1. 대상자의 특성 28 2. 헬스리터러시의 현황 34 3. 대상자의 특성별 헬스리터러시 39 4. 헬스리터러시에 영향을 미치는 요인 44 Ⅴ. 논의 및 고찰 1. 연구 결과에 대한 논의 48 2. 연구의 제한점 52 3. 연구의 의의 53 4. 헬스리터러시에 대한 고찰 53 Ⅵ. 결론 및 제언 60 참고문헌 64 부록 76 Abstract 97Maste

Immunohistochemical Analysis of Cancer Stem Cell Marker Expression in Papillary Thyroid Cancer

Cancer stem cell (CSC) markers have prognostic significance in various cancers, but their clinical significance in papillary thyroid carcinoma (PTC) has not been demonstrated. In this study, CSC markers expressed in PTC and their relationships with prognosis were evaluated. We constructed tissue microarrays for 386 PTC cases, divided it into 42 low risk cases and 344 intermediate risk cases according to the American Thyroid Association 2009 Risk Stratification System. Immunohistochemical staining of CSC markers (CD15, CD24, CD44, CD166, and ALDH1A1) was performed, and the proportion of stained cells and immunostaining intensity were evaluated to determine positive marker expression. The relationships between CSC marker expression and other clinicopathological parameters or survival were analyzed. CD15 expression was higher in PTC with intermediate risk than in PTC with low risk (29.4 vs. 11.9%, p = 0.017). According to a multivariate analysis, CD15, CD44, CD166, and ALDH1A1 positivity were independently associated with a shorter progression-free survival (PFS) (odds ratio [OR]: 1.929, 2.960, 7.485, and 3.736; p = 0.016, p = 0.026, p < 0.001, and p = 0.006, respectively). Higher N and cancer stage were the only other clinical factors associated with a shorter PFS (OR: 2.953 and 1.898, p = 0.011 and p = 0.034). Overexpression of CSC markers in PTC was associated with shorter PFS during follow-up. Immunohistochemical staining of CSC markers may provide useful information for predicting patient outcomes.ope

Study of cell therapy for ALS using neuronal stem cells from iPSCs with ectopic SOX2 expression

학위논문 (석사)-- 서울대학교 대학원 : 의과학과(의과학 전공), 2015. 8. 성승용.Amyotrophic Lateral Sclerosis (ALS), a regressive neuronal disease, results in the death of motor neurons. It is known as a deadly disease and most ALS patients die within five years of diagnosis due to its rapid progression, however, there are few treatments available for ALS. In order to attempt to develop a cell therapy system for the treatment of ALS, here, we use neuronal stem cells (NSCs) overexpressing the sex determining region Y-box 2 (SOX2). NSCs are differentiated from induced pluripotent stem cells (iPSCs), in particular, SOX2 is related to the differentiation into a neuronal lineage. Therefore, we focus on the overexpression of SOX2 in relation to the potential of NSCs to differentiate into motor neurons, and their effect on ALS in a mouse model. NSCs contain an inducible system to overexpress SOX2, which can be controlled by the use of doxycycline, therefore we gauged the differentiation potential by the level of SOX2 expression. According to quantitative RT-PCR and immunocytochemistry, motor neurons were more differentiated with increasing levels of doxycycline. To evaluate the functional activity of differentiated NSCs, they were transplanted into the ALS Cu/Zn superoxide dismutase 1 (SOD1) G93A transgenic mouse model (SOD1 G93A TG). The NSCs were injected at the junction between the brain and spinal cord, engrafting and surviving successfully, and further treated with doxycycline. A greater differentiation into motor neurons was expected in the group of treated mice, however the NSCs were differentiated into various other subtypes of neurons and glial cells, including astrocytes, after migration from the injection site to other areas of the brain and spinal cord. For the functional analysis of transplanted NSCs, we tested the movement and life span of SOD1 G93A TG mice engrafted with NSCs. Compared with the untreated control mice, the motion of the mice transplanted with NSCs was not improved, and their life span was not significantly extended. However, the NSCs prolonged the disease onset point. As the number of remaining cells reduced until death, the effectiveness of the NSCs was not carried over to the end of disease progression. With further experiments, considering the number of injection times and cells, the lifespan and motor function will likely be improved. Therefore, the NSCs that overexpressed SOX2 were well differentiated into motor neurons, although the ALS mouse did show extensive neural differentiation of differing types. In addition, NSCs were effective in slowing the ALS disease onset.Introduction 2 Material and Methods 6 Results 14 Discussion 34 References 37 Abstract in Korean 45Maste

Clinicopathological and Molecular Differences Between Gastric-type Mucinous Carcinoma and Usual-type Endocervical Adenocarcinoma of the Uterine Cervix

Background/aim: We investigated differences in the clinicopathological and molecular characteristics between gastric-type mucinous carcinoma (GMC) and usual-type endocervical adenocarcinoma (UEA). Patients and methods: We collected the clinicopathological information and performed targeted genomic sequencing analysis. Results: GMCs exhibited significantly deeper invasion depth, larger horizontal spread, more advanced stage, more frequent distant metastasis, and more frequent parametrial and vaginal extension. Disease-free survival time of GMC patients was significantly shorter than that of UEA patients. GMCs displayed mutant p53 immunostaining pattern, whereas UEAs exhibited p16 block positivity. GMCs harbored mutations in KRAS, TP53, NF1, CDKN2A, STK11, and ARID1A. One GMC exhibited MDM2 amplification. In contrast, UEAs harbored mutations in HRAS, PIK3CA, and BRCA2. Two UEAs were found to have novel TP53 mutations. Conclusion: GMC is associated with more aggressive behavior than UEA. Distinctive p53 and p16 immunostaining patterns enable differential diagnosis. GMC and UEA exhibit genetic heterogeneity with potentially actionable molecular alterations.ope

An Analysis of Travel Cost Equity for Commuters Using Public Transport in Seoul

학위논문 (석사)-- 서울대학교 대학원 : 환경대학원 환경계획학과, 2018. 8. 김성수.개인이 한 사회의 구성원으로서 일상의 사회경제활동을 영위하는 데 있어 교통은 필수적인 요소이다. 출발지에서 목적지까지 이동하는 과정에서 교통서비스를 이용하는 통행자가 경험하게 되는 이동성, 접근성, 경제성 등과 관련된 형평성의 가치는 더욱 강조된다. 최근의 교통형평성에 대한 논의는 주로 이동성 및 접근성의 측면에서 다뤄지고 있는 것으로 보인다. 그러나 개별 통행자가 지불하는 교통비용 등의 경제적인 측면 또한 가구별 소득지출과 경제부담 문제와도 연관된다는 점에서 형평성 분석에서 간과할 수 없는 지표이다. 대중교통은 통근통행을 포함하는 필수통행에서 자가용 승용차를 이용할 수 없는 통행자가 선택하는 대안으로 형평성 측면에서 중요하게 인식되는 교통수단이다. 본 연구에서는 서울시를 대상으로 대중교통 통근자의 형평성을 분석하였다. 2010 가구통행실태조사 자료의 통근통행 정보를 기반으로 통행에 소요된 시간비용과 운임을 추출한 후, 일반화비용 관점의 통근비용을 산정하였다. 이를 바탕으로 수평적 형평성 및 수직적 형평성에 대한 분석을 진행하였다. 2010년 운임체계를 기준으로 기본운임 인상, 기본구간 축소, 추가요금 인상 및 균일요금제로 구성된 총 4가지의 운임 시나리오를 설정하였다. 시나리오 비교분석을 통해 대안별 운임수준에 따른 로렌츠곡선과 지니계수 변화에 따른 형평성 개선 방안을 제안하고자 하였다. 수평적 형평성은 시간비용 및 운임으로 구성되는 통근비용과 함께 단위거리운임의 관점에서 대중교통 통근자의 불평등 정도를 알아보았다. 수직적 형평성에서는 통근비용, 단위거리운임과 운임부담비율 분석을 수행하여 하위소득계층을 포함하는 대중교통 통근자 인구집단에 대한 형평성의 변화 양상을 비교하였다. 통근비용 기반의 분석에서 수평적 형평성과 수직적 형평성의 결과는 반대로 나타났다. 그러나 단위거리운임 분석에서는 수평적 형평성과 수직적 형평성 모두 추가요금 인상 시나리오가 가장 공평한 대안인 반면, 균일요금제는 가장 불공평한 대안으로 나타났다. 또한 운임부담비율을 통해 통근자의 소득 대비 교통비용의 부담 정도를 측정하였다. 중위소득을 이용하여 소득계층을 구분하고 하위소득계층에 해당하는 경계값을 산정하였으며, 추가요금 인상 대안이 경계값과 대응하는 누적 하위소득계층비율의 크기가 가장 작게 나타난 시나리오였다. 이러한 결과는 통근자에 대한 소득과 탑승거리 간의 관계가 영향을 미친 것으로 보인다. 서울시 대중교통 통근자의 형평성 문제를 논의하는데 있어서 단위거리운임과 운임부담비율을 고려하는 통합적 관점의 접근이 요구된다. 운임 시나리오 분석 결과를 보면, 수평적 형평성의 통근비용 분석결과를 제외하면 공통적으로 추가요금 인상 방안이 전체 통근자 집단 및 하위소득계층이 지불 또는 부담하는 운임수준이 가장 형평한 대안인 것으로 나타났다. 이러한 점에서 서울시 대중교통 통근자의 형평성을 개선하기 위해서는 추가요금 인상에 대한 고려가 필요하다. 본 연구에서는 서울시 대중교통 통근자의 형평성을 분석하기 위해 통근비용을 산정하고, 운임 시나리오에 따른 형평성의 변화를 보았다. 그러나 서울시를 공간적 범위로 한정하여 수직적 형평성에서 운임 시나리오별 뚜렷한 차이가 나타나지 않았다. 향후 수도권으로 연구범위를 확대할 경우 보다 유의미한 분석결과를 얻을 수 있을 것으로 예상된다. 또한, 자료의 분석 시점이 2010년이기 때문에 대중교통 통근자의 최근 현황을 반영하기 어려우며, 소득 및 통행시간 등의 산정이 개별 응답자의 설문에 근거한 추정치라는 점에서 정확한 정보를 적용했다고 보기 어렵다. 향후 연구에서는 이러한 한계점을 보완할 필요가 있다고 판단된다.Transportation equity has been highlighted as transport service serves an essential role for members of society to travel to certain areas by transport modes. Transportation makes residents get their own primary right of mobility move to different regions to participate in socio-economic activities. The value of equity associated with mobility, accessibility, or economic efficiency has been considered one of the most fascinated research fields recently. Although recent discussions on transport equity seem to be mainly concentrated on mobility and accessibility matters, economic aspects involving travel cost would be also important in that they are related to household income expenditure and economic burden issues. Public transport is a basic and significant service for passengers who are not able to drive cars for their trips, including commuting. In this paper, commuters using public transport are observed to analyze transport equity. Time cost and fares extracted from the 2010 Household Travel Survey are examined to estimate travel costs. Based on 2010 fare system, four fare scenarios are establishedincrease in basic fare, reduction in distance of basic fare for long distance trip, increase in additional fare, and flat fare regardless of travel distance. Under these scenarios, fares charged for individuals are compared with Lorenz curve and Gini coefficient respectively. Equity analyses for travel cost show the extent of inequality over commuters. Thus, the concept of charge per distance is applied to measure fairness of fare payment. In addition, affordability analyses are conducted to gauge practical household burden of fare expenditure, especially in the viewpoint of vertical equity. For that, household income information is extracted to calculate the median income, which is utilized to set the income threshold for low-income group. The results of travel cost composed of time cost and fare indicate the opposite features of horizontal equity and vertical equity. The former represents the flat fare system is the best, while the latter turns up the additional fare increase is good one. Nevertheless, increase in additional fare option is the most equitable commonly both charge per distance vertical equity fare scenarios. These trends imply that the weak relationship between income level and travel distance in the study area could have an effect on the equity analyses process. An integrated approach with charge per distance and affordability is required when equity issues are under discussion for commuters. Among fare scenarios, except for travel cost in horizontal equity, the additional fare increase explains that it is the most advisable way to resolve equity problems for not only the entire commuters but also lower income bracket. Hence, rather than just focusing on basic fare option, the increase in additional fare should be considered in order to ease inequality and improve transport equity for public transport users in Seoul. Fare scenarios based on travel cost are evaluated to analyze transport equity and to proposes the best scenario to improve equity level for public transport commuters. However, there are several limitations due to spatial and data characteristics. Scenarios in vertical equity did not demonstrate critical differences. However, more significant analyses would be possible if the research will be expanded to the Seoul metropolitan area, including Incheon, and Gyeonggi-do province. Last but not least, it is difficult to reflect the current status of commuters since the data used in this study is surveyed in 2010. There is inaccuracy in the survey data, such as household income and travel time, as they were dependent on individual respondents estimation. Thus, the parameters used are not enough to reflect commuters behaviors and their own features. In the future, further equity-related studies should be conducted to overcome the limits of this study.제 1 장 서론 1 제 1 절 연구의 배경 및 목적 1 제 2 절 연구의 범위 3 제 2 장 관련 이론 및 선행연구의 고찰 5 제 1 절 관련 이론 5 1. 교통형평성 5 (1) 수평적 형평성 5 (2) 수직적 형평성 6 2. 로렌츠곡선 및 지니계수 7 제 2 절 관련 선행연구 8 1. 형평성 이론 및 적용 8 2. 교통형평성 분석 10 (1) 수평적 형평성 10 (2) 수직적 형평성 12 (3) 수평적 형평성 및 수직적 형평성 14 (4) 운임부담비율 15 제 3 절 시사점 16 제 3 장 연구방법론의 정립 19 제 1 절 대중교통 통근비용의 추정 19 제 2 절 로렌츠곡선 및 지니계수 21 1. 통근비용 21 2. 단위거리운임 24 3. 운임부담비율 26 제 4 장 자료의 구축 29 제 1 절 통근비용의 산정 29 1. 서울시 대중교통 통근자 29 2. 통행시간의 구분 및 계산 31 (1) 차내시간, 차외시간 31 (2) 시간비용 및 운임 33 3. 대중교통 운임 기준 35 제 2 절 자료의 특성 분석 36 1. 통근통행 특성 36 2. 통근자의 사회경제적 특성 39 제 5 장 대중교통 통근비용의 분석결과 44 제 1 절 운임 시나리오의 설정 44 제 2 절 수평적 형평성 48 1. 통근비용, 시간비용 및 운임 48 2. 탑승거리별 단위거리운임 50 제 3 절 수직적 형평성 52 1. 소득수준에 따른 통근비용, 시간비용 및 운임 52 2. 소득수준별 단위거리운임 54 3. 운임부담비율 57 제 6 장 결론 62 제 1 절 연구의 요약 62 제 2 절 연구의 한계 및 향후 과제 64 참고문헌 65 부록 70 대중교통 통근자의 차내시간 분포 70 대중교통 통근자의 탑승거리 분포 70 대중교통 통근자의 통근비용 분포 71 대중교통 통근자의 시간비용 분포 71 하위소득계층의 탑승거리 72 중위소득계층의 탑승거리 72 상위소득계층의 탑승거리 72 운임 시나리오별 운임부담비율 73 Abstract 74Maste